title: Decreased expression of nuclear p300 is associated with disease progression and worse prognosis of melanoma patients.
abstract: BACKGROUND
  Genomic instability due to UV radiation is one of the leading causes for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA repair and maintenance of genomic integrity. The present study was performed to analyze the correlation between p300 expression, melanoma progression and patient survival.
  
  
  METHODS
  Tissue microarray and immunohistochemical analysis was employed to study the expression of p300 in melanoma patients. A total of 358 melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis, and receiver-operating characteristic curves, were used to elucidate the prognostic significance of p300 expression.
  
  
  RESULTS
  Our results demonstrate that p300 is expressed in both nucleus and cytoplasm but the nuclear expression of p300 is predominant. The progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma was associated with decreased nuclear and increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain in cytoplasmic p300 was correlated with the progression of melanoma from AJCC stage II to stage III, which requires the migration and metastasis of cancer cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and increase in cytoplasmic p300 expression correlated with worse survival of melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the patient survival independent of AJCC stage, age and gender.
  
  
  CONCLUSIONS
  Loss of nuclear p300 expression is an indicator of worse patient survival and is an independent prognostic marker for melanoma.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.forename: Yabin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sjoestroem
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000235:genetics* / Q000503:physiopathology*; D016016:Proportional Hazards Models; D012372:ROC Curve; D046888:Tissue Array Analysis; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor